The long range objective is to utilize isolated nucleoli of the Novikoff ascites tumor and other rat tissues for study of the synthesis and processing of ribosomal RNA and ribosomes in vitro. This will require dissection and recombination of the many components of the system: DNA templates, RNA polymerase, RNA methylases, ribonucleases, ribosomal proteins, etc. The mechanisms of control of these reactions (both natural metabolic regulation and selective inhibition by antimetabolites) and their application to malignant growth are being given special consideration. The immediate objectives are to pursue the characterization of the nucleolar ribosomal RNA methylases and their role in the processing of pre-ribosomal RNA. We have demonstrated that the activity of ribosomal RNA methylases is subjected to modulation by RNA metabolites, and that the status of regulation of ribosomal RNA methylases is considerably different between tumor and normal tissues. Many inhibitors shown to affect the activity of tumor enzymes were inactive against liver enzymes. These facts provide a desirable basis for seeking ribosomal RNA methylase inhibitors as antitumor agents. S-adenosylmethionine synthetase, the enzyme providing substrate for RNA methylases, is also under vigorous investigation.